NFκB-Independent Signaling to the Cyclin D1 Gene by Rac

Abstract

In this report we characterize the mechanism of Rac‑mediated cyclin D1 gene expression in mouse embryonic fibroblasts. Activated Rac strongly stimulated cyclin D1 gene transcription but did not alter the half‑life of cyclin D1 mRNA. Inhibition of NFkB signaling with the IkB super‑repressor blocked the Rac‑dependent expression of cyclin D1 mRNA, and this effect was selective since ERK‑dependent cyclin D1 mRNA induction was minimally affected by super‑repressor expression. However, we found that p65 activity in this system was induced by serum and not by activated Rac. Moreover, mouse cyclin D1 promoter‑luciferase assays showed that Rac stimulated cyclin D1 gene expression without activating NFkB and that an essential Rac‑regulated promoter element is located far upstream or downstream of the cyclin D1 transcription start site. We conclude that, in MEFs, Rac-mediated induction of cyclin D1 mRNA requires activation of a parallel NFkB pathway whereas ERK induces cyclin D1 transcription independent of NFkB.